By Professor Charles ffrench-Constant
Director of the Edinburgh MS Research Centre

Professor Charles ffrench-Constant: "Huge difference"

The Edinburgh MS Research Centre, a partnership with Edinburgh University, has been founded by the MS Society Scotland following a generous donation from author JK Rowling.

Its aim is to make discoveries about myelin and translate those discoveries into drug treatments that promote myelin repair.

It is significant that we now have a range of treatments that target one important element of multiple sclerosis - the inflammatory process.

Beta interferons, glatiramer acetate and natalizumab work by dampening the inflammation that exists in the early stages of MS.

Treatments such as these have been brought about by great advances in our understanding of how the immune system works in MS.

Currently, however, there are no treatments that can help with the repair and protection of myelin to prevent or reduce nerve fibre loss in MS, and finding an effective treatment to prevent and try to reverse progressive disease is now the highest priority.

MULTIPLE SCLEROSIS

MS is a condition in which myelin wrapped around nerve fibres in the brain and spinal cord is lost

The concentrated areas of myelin loss are called plaques - also known as lesions or scars

The word "sclerosis" comes from the Greek "skleros" meaning hard, with the many hard areas of scarring giving rise to the name "multiple sclerosis"

In MS, the damage to myelin is caused by inflammation - active inflammatory cells from the body's own immune system infiltrate the central nervous system (the brain and spinal cord)

Scientists do not yet know why these active cells get out of the blood where they belong and enter the brain, causing the loss of myelin

Myelin matters because it enables signals to travel along the nerve fibres. Interruption and loss of signalling can cause attacks of numbness, loss of vision, weakness, bladder problems and problems with movement - the symptoms associated with MS

Myelin also matters because it protects the nerve fibres themselves

We want to know how to promote remyelination, and thereby develop a treatment that can help myelin repair. That's the next key scientific question in MS treatment.

This will take patience, but already we have some discoveries on which we can build.

At the Edinburgh MS Research Centre, we will try to unravel the mysteries of myelin.

We know there are two main ways that myelin is damaged in MS by the inflammatory cells that infiltrate the central nervous system.

One is where the myelin is attacked, but the cells that make myelin (called oligodendrocytes) survive, and the other is where these cells themselves are attacked and destroyed.

We know that the way myelin is damaged will be different from person to person. But in any one person, it will be the same process.

We also know that the treatments needed to promote remyelination will be different for each of these processes.

So, if the myelin-making cells are still present in the brain, we must try to reactivate them to repair. If they are destroyed, we must either replace them by transplantation, or generate new cells from within the brain itself.

One of the most exciting discoveries of recent years is the finding that the adult brain contains stem cells throughout life.

Adult stem cells

So, as transplantation carries risk, it would be preferable to use the brain's own stem cells to generate the new cells needed to make myelin.

Along with the discovery of "adult" stem cells, scientists have also learned that the central nervous system has an in-built or innate ability to repair myelin itself.

Under a microscope, you can see that there is some remyelination in early stage MS. The body's own repair mechanisms are forming new myelin - seen as thinner rings than the myelin coating it replaces, but sufficient to protect the nerve fibres.

This natural remyelination can be very extensive in many people with MS. It varies from person to person.

The problem is very complicated, and although we know that particular cells are key in remyelination, we also need to look more widely at the environment in which these cells are situated to identify what helps them, and what inhibits them.

It is a very tough challenge and to meet it, we and other scientists are exploring multiple approaches to try to discover more.

To help make discoveries about myelin, other important work will take place at Edinburgh.

We will try to develop better experimental models of MS so scientists can test their ideas.

Studies also need to use human cells. The Edinburgh MS Research Centre will generate human oligodendrocytes from stem cells, and collaborate with others to examine post-mortem tissue donated by people with MS.

Work will also take place using sophisticated MRI. Scientists have a challenge ahead to identify features that can be seen on MRI that can be matched up with the different patterns of myelin damage and remyelination in MS.

The vision for the Edinburgh MS Research Centre is to make discoveries that go way beyond national boundaries

It is a natural question for people living with MS now to ask how long it will take to have a treatment for myelin repair in MS. The answer is that it takes on average about 10 to 12 years to take a target to the clinic.

That is, it takes about a decade from discovering a drug target to producing a drug, and first the centre will need to identify targets - for example, a factor that promotes growth of myelin.

The Edinburgh MS Research Centre will also be working to improve the care and treatment of people with MS now.

The centre will try to take advantage of the new therapies that drug companies are currently developing and help run the clinical trials needed to establish their effectiveness.

The centre will recruit additional neurologists to work directly with people with MS in the clinic at the Western General Hospital.

The centre will be a major hub of MS research into myelin repair. Other centres also have myelin repair as their aim - the MS Society Cambridge Centre for Myelin Repair, and other centres internationally.

'Huge difference'

We all share common goals and we all interact, with a mixture of competition and collaboration ensuring that advances come as quickly as possible - a bit like a professional bicycle race, where everyone wants to finish as fast as possible, but knows that they must work with others to stay ahead of the pack.

Having said that, I believe that Scotland is uniquely placed to advance and deliver in MS research. Scotland has one of the strongest set of stem cell biologists anywhere in the world, and there is a major new initiative here called the Scottish Centre for Regenerative Medicine, of which our centre is a part.

There is no other place that I am aware of in the UK that is trying to put all of its stem cell biologists and all the clinicians interested in regenerative medicine in the same building. It is something that could make a huge difference to medicine.

It is fitting, too, that Scotland has such a centre for MS research. Scotland is thought to have the highest rate of MS in the world.

The vision for the Edinburgh MS Research Centre is to make discoveries that go way beyond national boundaries.

• This piece is based on an article first published in MS Matters, the MS Society's magazine for people living with MS.

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